Karl Herrup

Solving all of human disease in alphabetical order Alzheimer's, ataxia-telangiectasia, autism. Professional iconoclast. International outlook. Politics separate

[Karl Herrup @KarlHerrup]

Some of us might take issue with characterizing it as “pretty solid”. I actually wrote an entire book unpacking the evidence and while there were a few sticks left standing here and there, the evidence in support of the current biomarkers came away looking flimsy at best.

[Simon Mead @smead2]

@ProfRobHoward @pash22 @MGarrett1959 @PhilAlz @ajlees @DavidJonesBrain @LonSchneiderMD @nvillain_alz @DanClintonRN @LogarithmicDis @gregggonsalves @DrTFromKC @AlbertoEspay @Kariem_Ezzat @MadhavThambiset @matthewherper @seb_walsh @JosephTherr @dmrind @Scott_M_Reid @EWidera @RenegadeSynapse @KasperKepp @Jennife10651535 @pxrobbo @MemoryDoc @metapredict @CorriveauNick @eturnermd1 @kateeeemily @StefanoSensi14 @VincentPlanche @ayton_scott @reshmagar @KarlHerrup @GiovanniFrisoni @macesari @geoperry @samgandy @Gill_Livingston @andrea_sturchio @AndaloussiLab @rkhamsi @r_merrick @schrag_matthew @kathy_y_liu @naomikresge Much more than a guess imo and beyond the groups you characterise danger of echo chamber view here. Decades of research have established causes and biomarkers of Alzheimer’s disease. If you discard this field of research I can see why you would be a skeptic, but it’s pretty solid

[Karl Herrup @KarlHerrup]

Well, here we go. Fasten your seatbelts. This is going to be a rough ride.

[Ash Paul @pash22]

@AlbertoEspay @ajlees @KasperKepp @seb_walsh @nvillain_alz @masterlongevity @DanClintonRN @ProfRobHoward @gregggonsalves @PhilAlz @DrTFromKC @smead2 @DavidJonesBrain @LonSchneiderMD @Kariem_Ezzat @MadhavThambiset @matthewherper @JosephTherr @dmrind @Scott_M_Reid @EWidera @RenegadeSynapse @LogarithmicDis @Jennife10651535 @pxrobbo @MemoryDoc @metapredict @CorriveauNick @eturnermd1 @kateeeemily @StefanoSensi14 @VincentPlanche @ayton_scott @reshmagar @KarlHerrup @GiovanniFrisoni @macesari @geoperry @samgandy @Gill_Livingston @andrea_sturchio @AndaloussiLab @rkhamsi @r_merrick @schrag_matthew @kathy_y_liu @naomikresge @MedicareGov @JAMANetwork Major US health systems expect to offer Alzheimer's drug Leqembi in a few months
https://t.co/BOElOamBgt via @JDSteenhuysen et al

[Karl Herrup @KarlHerrup]

We agree. I made the tau comment mostly because I worry about the fuzzy way we define AD (made even worse by Jacks presentation at #AAIC23 ). We are quick to ascribe causality to correlation and need to be more careful.

[Nicolas Villain / Moved to LinkedIn & BlueSky @nvillain_alz]

@KarlHerrup @KarlHerrup, I just want to be sure we align, here. We all agree that not all dementia involving tau agregates are AD, right?

https://t.co/eZDiwP7khm

[Karl Herrup @KarlHerrup]

I was trying to point out that if you reject amyloid as a defining feature of AD (which I do), dementia resembling AD can also be induced by tau alone. The clinical presentations in AD and FTD are of course different but I submit there is lots of biology left to work out

[Karl Herrup @KarlHerrup]

The problem is the assertion that when the tau stage of AD is reached there is always amyloid. If AD is defined by amyloid this is not an informative statement. Amyloid has to be present or it isn’t AD.

[Trey Bateman @RenegadeSynapse]

@nvillain_alz @KarlHerrup I’m with @nvillain_alz here; I’m not entirely sure I understand how this is a problem. We all recognize non-AD tauopathy in the form of FTLD-tau, and I’m unaware of anyone to suggest all tauopathy is AD or how MAPT mutations are relevant for AD neuropathological change.

[Karl Herrup @KarlHerrup]

Help me out here. If AD is defined by amyloid then you can’t have *any* stage of the disease without amyloid. Mutations in Mapt show that you can have tau-driven dementia. But these dementias are not AD by definition. So isn’t this a bit of circular logic?

[Nicolas Villain / Moved to LinkedIn & BlueSky @nvillain_alz]

@DanClintonRN @LonSchneiderMD @AlbertoEspay @Kariem_Ezzat @pash22 @smead2 @MadhavThambiset @ProfRobHoward @matthewherper @DrTFromKC @seb_walsh @PhilAlz @JosephTherr @dmrind @Scott_M_Reid @EWidera @RenegadeSynapse @gregggonsalves @LogarithmicDis @KasperKepp @Jennife10651535 @pxrobbo @MemoryDoc @metapredict @CorriveauNick @DavidJonesBrain @eturnermd1 @kateeeemily @StefanoSensi14 @VincentPlanche @ayton_scott @reshmagar @KarlHerrup @GiovanniFrisoni @macesari @geoperry @samgandy @Gill_Livingston @andrea_sturchio @AndaloussiLab @rkhamsi @r_merrick @schrag_matthew @kathy_y_liu @naomikresge @MedicareGov @JAMANetwork @ManlyEpic @KcD_PhD It's not a theory, Dan, it's a scientific fact, a piece of evidence, a constant observation: slowly progressing Alzheimer's tauopathy reaching the very latest stages of dementia, being the "major killer" underlined in 1976, doesn't exist without amyloid.

[Karl Herrup @KarlHerrup]

Thank you

[Karl Herrup @KarlHerrup]

@AdrianoAguzzi @smead2 @AlbertoEspay @Kariem_Ezzat @andrewmstern @PhilAlz @nvillain_alz @JosephTherr @dmrind @DanClintonRN @MadhavThambiset @LonSchneiderMD @pash22 @Scott_M_Reid @EWidera @seb_walsh @DrTFromKC @RenegadeSynapse @gregggonsalves @LogarithmicDis @ProfRobHoward @KasperKepp @Jennife10651535 @pxrobbo @MemoryDoc @metapredict @CorriveauNick @DavidJonesBrain @eturnermd1 @kateeeemily @StefanoSensi14 @VincentPlanche @ayton_scott @reshmagar @GiovanniFrisoni @macesari @geoperry @samgandy @Gill_Livingston @andrea_sturchio @AndaloussiLab @rkhamsi @r_merrick @schrag_matthew @kathy_y_liu @naomikresge @matthewherper @MedicareGov @JAMANetwork @ManlyEpic I agree with the L = A-R equation, but speed of R is still not relevant. The extent matters (maybe) but whether we get to 20 centiloids slowly or rapidly, the kinetics at equilibrium are going to be the same.

[Karl Herrup @KarlHerrup]

@smead2 @AlbertoEspay @Kariem_Ezzat @andrewmstern @PhilAlz @nvillain_alz @JosephTherr @dmrind @DanClintonRN @MadhavThambiset @LonSchneiderMD @pash22 @Scott_M_Reid @EWidera @seb_walsh @DrTFromKC @RenegadeSynapse @gregggonsalves @LogarithmicDis @ProfRobHoward @KasperKepp @Jennife10651535 @pxrobbo @MemoryDoc @metapredict @CorriveauNick @DavidJonesBrain @eturnermd1 @kateeeemily @StefanoSensi14 @VincentPlanche @ayton_scott @reshmagar @GiovanniFrisoni @macesari @geoperry @samgandy @Gill_Livingston @andrea_sturchio @AndaloussiLab @rkhamsi @r_merrick @schrag_matthew @kathy_y_liu @naomikresge @matthewherper @MedicareGov @JAMANetwork @ManlyEpic @KcD_PhD I’ve heard this idea before - the importance of speed of removal - but I don’t get it. I can think of no biological reason why speed should make a difference. This is not like pulling off a bandaid.

[Karl Herrup @KarlHerrup]

Poster is online. Feel free to download.

[Paul Jerome Lamont @PAULJLAMONT]

@KarlHerrup Prof , do you have a full picture of your poster ? Thank you

[Karl Herrup @KarlHerrup]

Only a few hours left to see one of the best posters at #AAIC. Oligodendrocytes rule!!4

[Karl Herrup @KarlHerrup]

@matthewherper @MadhavThambiset @KasperKepp @LogarithmicDis @LonSchneiderMD @pash22 @ProfRobHoward @nvillain_alz @DanClintonRN @gregggonsalves @Jennife10651535 @pxrobbo @seb_walsh @MemoryDoc @dmrind @metapredict @DrTFromKC @JosephTherr @PhilAlz @CorriveauNick @RenegadeSynapse @DavidJonesBrain @ChuckGartland1 @eturnermd1 @kateeeemily @AlbertoEspay @StefanoSensi14 @VincentPlanche @ayton_scott @reshmagar @GiovanniFrisoni @macesari @geoperry @samgandy @Gill_Livingston @Kariem_Ezzat @andrea_sturchio @AndaloussiLab @rkhamsi @r_merrick @schrag_matthew @kathy_y_liu @naomikresge @prof @WesselsAlette @LillyPad @MedicareGov @US_FDA @adamfeuerstein @statnews It’s worth noting that the 27% figure for Leqembi is not relative risk. It’s relative decline at 18 months. On Leqembi everyone gets worse. On statins more people avoid disease or death. I think that makes the analogy a bit misleading.

[Karl Herrup @KarlHerrup]

Statistically significant but clinically trivial slowing of #Alzheimer’s decline is not “improvement” Slightly less bad doesn’t mean good. And the hazards are frighteningly real. I am quite worried that there will be needless deaths. I sincerely hope I’m wrong.

[Karl Herrup @KarlHerrup]

Sorry, I’ve got to weigh in here. Today’s was an inevitable decision - baked into the cake a while ago when #Leqembi’s predecessor, #Aduhelm, was given the fast track by the FDA based on lowering amyloid.

[Jessica Adams @RxRegA]

Is there an FDA-approved drug to maintain mental function in Alzheimer's? I see this tweet from FDA (pic) and did a double take to ask this question.
Where I'm coming from I know the recent beta-amyloid drugs are still pending clinical outcomes. I thought at most you could say they show promise in slowing overall decline, which is different from saying they maintain function. So what drug maintains function?
So, I think I'll click the link to find out. The link take me to a page with brochure that mentions aducanumab. No mention of lecanemab. I guess the brochure is old? It also mentions cholinesterase inhibitors. Maybe it's the latter.
However, I wouldn't know from the brochure, which doesn't even mention the PIs or link to clinical information.
How helpful is this? Is this really where FDA should be focused? Can they keep up? Or can we just ask our doctors and use other sources?
Maybe I'm a stickler, but I expect more from a science-based agency, and I don't think they can keep up on brochures like this or if it's even their job.

[Karl Herrup @KarlHerrup]

@AE_MD @LonSchneiderMD Enjoy. But will you wear a shirt?

[Karl Herrup @KarlHerrup]

I will be at #AAIC23 in Amsterdam wearing this. If you're coming & would like one, DM me with your size (S, M. L, XL,...). I need to order by Monday (3 July) so hurry. They cost me US$16 each, but they're free to attendees who promise to wear them (donations welcome of course)

[Ali Ezzati @AE_MD]

@LonSchneiderMD @KarlHerrup Tbf, this is getting way more exciting than science! I'll be there for the drama 🍿🍿🍿

[Karl Herrup @KarlHerrup]

(talking about my new Maserati of course)

[Karl Herrup @KarlHerrup]

@suzanahh What??!!!??!!!